Alkanes water

Surface SHG [4.307] produces frequency-doubled radiation from a single pulsed laser beam. Intensity, polarization dependence, and rotational anisotropy of the SHG provide information about the surface concentration and orientation of adsorbed molecules and on the symmetry of surface structures. SHG has been successfully used for analysis of adsorption kinetics and ordering effects at surfaces and interfaces, reconstruction of solid surfaces and other surface phase transitions, and potential-induced phenomena at electrode surfaces. For example, orientation measurements were used to probe the intermolecular structure at air-methanol, air-water, and alkane-water interfaces and within mono- and multilayer molecular films. Time-resolved investigations have revealed the orientational dynamics at liquid-liquid, liquid-solid, liquid-air, and air-solid interfaces [4.307]. 

Alog P difference between log P in octanol-water and alkane-water... 

Traditional octanol-water distribuhon coefficients are shll widely used in quan-titahve structure-achvity relationship (QSAR) and in ADM E/PK studies. However, alternahve solvent systems have been proposed [80]. To cover the variabihty in biophysical characterishcs of different membrane types a set of four solvents has been suggested, somehmes called the critical quartet [81]. The 1,2-dichloroeth-ane-water system has been promoted as a good alternative to alkane-water due to its far better dissolution properties [82, 83], but may find little applicahon because of its carcinogenic properties. 

With only few exceptions, most log P programs refer to the octanol-water system. Based on Rekker s fragmental constant approach, a log P calculation for aliphatic hydrocarbon-water partitioning has been reported [96]. Another more recent approach to alkane-water log P and log D is based on the program VolSurf [97]. It is believed that these values may offer a better predictor for uptake in the brain. 

Caron, G Ermondi, G. Calculating virmal log P in the alkane/water system (logPait) and its derived parameters AlogP/i ait and logDJ. /. Med. Chem. 2005, 48, 3269-3279. 

Wohnsland, F., Faller, B. High-throughput permeability pH profile and high-throughput alkane/water log P with artificial membranes. J. Med. 

A, B and V are constant for a given solute (Eig. 12.4 shows the value of A, 0.78, for atenolol). This means that the balance between intermolecular forces varies with the system investigated as would be expected from a careful reading of Section 12.1.1.3. This can also be demonstrated by using a completely different approach to factorize log P, i.e. a computational method based on molecular interaction fields [10]. Volsurf descriptors [11] have been used to calculate log P of neutral species both in n-octanol-water and in alkane-water [10]. 

It is our opinion that, among isotropic systems, alongside the standard octanol-water, the alkane-water system (partihoning between water and different alkanes is relahvely independent of the alkane used [14]) is the only system that can be successfuUy used in ADMET predichon, because of its completely different nature from octanol-water. The situahon is much more confused for arhsohopic systems (see Ref. [7] for a brief review) since no standard system has been defined to date. 

One of the first studies to predict log P by using potential energy fields calculated using the GRID and CoMFA approaches was done by Kim [60]. The author investigated H, CH3 and H2O probes, and calculated the best models using the hydro-phobic probe H2O for relatively small series (20 or less compounds each) of furans, carbamates, pyridines and pyrazines. A similar study was performed by Waller [61] who predicted a small series of 24 polyhalogenated compounds. Recently, Caron and Ermondi [62] used a new version of Cruciani s software, VolSurf [63], to predict the octanol-water and alkane-water partition coefficients for 152 compounds with r = 0.77, q = 0.72, SDEP = 0.60 for octanol-water and r = 0.76, q = 0.71, SDEP = 0.85 for alkane-water. 

One of the likely reasons octanol-water gained such a widespread use is its amphiprotic character, i.e. its abiUty to serve as an H-bond donor and acceptor while, for example, alkane-water systems are inert in that sense, from the point... 

The difficulties and low-throughput nature of the experimental dual determination, especially in alkane-water systems, the development of other techniques more amenable to automation, as well as more refined computational approaches for octanol-water systems, aU have contributed to Umit the use of the alkane-water system as a second bulk-phase system. However, efforts have been devoted to the development of log (alkane) computational prediction methods by Rekker et al. [13] as well as Caron and Ermondi [14]. 

Figure 7.11 Intrinsic permeabilities versus alkane-water partition coefficients for drugs PAMPA filters soaked with alkane [509].

It is also quite interesting that lipid model 4.0 may be used to obtain alkane partition coefficients at high-throughput speeds, as suggested by Faller and Wohnsland [509,554], It is also interesting to note that since our Pe are corrected for membrane retention, the slope in Fig. 7.11 corresponding to the dashed line (our data) is 1.0, whereas the data not corrected for retention (solid line) show a lesser slope. This may not matter if the objective is to obtain alkane-water log Kp values at high speeds. 

Figures 7.31a-c clearly show that after some critical soy content in dodecane, Pe values decrease with increasing soy, for both sink and sinkless conditions. [This is not due to a neglect of membrane retention, as partly may be the case in Fig. 7.23 permeabilities here have been calculated with Eq. (7.21).] Section 7.6 discusses the Kubinyi bilinear model (Fig. 7.19d) in terms of a three-compartment system water, oil of moderate lipophilicity, and oil of high lipophilicity. Since lipo-some(phospholipid)-water partition coefficients (Chapter 5) are generally higher than alkane-water partition coefficients (Chapter 4) for drug-like molecules, soy lecithin may be assumed to be more lipophilic than dodecane. It appears that the increase in soy concentration in dodecane can be treated by the Kubinyi analysis. In the original analysis [23], two different lipid phases are selected at a fixed ratio (e.g., Fig. 7.20), and different molecules are picked over a range of lipophilicities.

Seiler [250] proposed a way of estimating the extent of hydrogen bonding in solute partitioning between water and a lipid phase by measuring the so-called A log P parameter. The latter parameter is usually defined as the difference between the partition coefficient of a solute measured in the octanol-water system and that measured in an inert alkane-water suspension AlogP = log Kp oet — log Kp aik. 

Patel S, Brooks CL (2006) Revisiting the hexane-water interface via molecular dynamics simulations using nonadditive alkane-water potentials. J Chem Phys 124(20) 204706... 

A log P Difference between log P in octanol/water and alkane/water log D Logarithm of the distribution coefficient in octanol/water at pH 7.4 log P Logarithm of the partition coefficient in octanol/water (for neutral species)... 

Faller and Wohnsland [18, 19] developed the PAMPA assay using phospholipid-free hexadecane, supported on 10 pm-thick polycarbonate filters, and were able to demonstrate interesting predictions. Their PAMPA method appeared to be a satisfactory substitute for obtaining alkane/water partition coefficients, which are usually very difficult to measure directly, due to the poor solubility of drug molecules in alkanes. Apparently, membrane retention was not measured. 

Hafkenscheid, T.L., Tomlinson, E. (1983) Correlations between alkane/water and octan-l-ol/water distribution coefficients and isocratic reversed-phase liquid chromatographic capacity factors of acids, bases and neutrals. Int l. J. Pharmaceu. 16, 225-239. 

Mackay, D., Shiu, W.Y., Wolkoff, A.W. (1975) Gas chromatographic determination of low concentrations of hydrocarbons in water by vapor phase extraction. ASTM STP 573, pp. 251-258, Am. Soc. Testing and Materials, Philadelphia, Pennsylvania. Macknick, A.B., Prausnitz, J.M. (1979) Vapor pressures of high-molecular-weight hydrocarbons.. /. Chem. Eng. Data 24, 175-178. Mac/ynski. A., Wioeniewska-Goclowska, B., Goral, M. (2004) Recommended liquid-liquid equilibrium data. Part 1. Binary alkane-water systems. J. Phys. Chem. Ref. Data 33, 549-577. 

J. As with the alkane - water systems, the interaction parameters for the aqueous liquid phase were found to be temperature - dependent. However, the compositions for the benzene - rich phases could not be accurately represented using any single value for the constant interaction parameter. The calculated water mole fractions in the hydrocarbon - rich phases were always greater than the experimental values as reported by Rebert and Kay (35). The final value for the constant interaction parameter was chosen to fit the three phase locus of this system. Nevertheless, the calculated three-phase critical point was about 9°C lower than the experimental value. 

Experimental solubility data are available for some higher alkane - water systems (see, for example, Skripka et al., (38)). However, these data either cover only a very limited temperature range or contain results for one phase only. No attempt has been made to determine the interaction parameters for water - hydrocarbon systems where the hydrocarbon is larger than n-octane. 

Three-Phase Loci. Figure 11 shows the three-phase loci for the alkane - water systems. No experimental three-phase data were available in the literature for the ethane - water binary. 

Wohnsland and Faller ([175] performed measurements using a thin (9-10 //in) supported, phospholipid-free hexadecane layer. To validate their model, they used 32 well-characterized chemically diverse compounds. The permeability values obtained with their model could be correlated with known human absorption values if the maximum permeability obtained at different pH was taken into account. However, several disadvantages are related to this method. For hydrophilic drugs, hexadecane by itself has an increased barrier function in comparison with membranes. In addition, the hexadecane layers are not very stable, which makes this assay difficult to apply as a routine screening method. The advantage of this PAMPA setup is that it appears to be a satisfactory substitute for obtaining alkane-water partition coefficients, which are usually very difficult to measure directly, due to the poor solubility of drug molecules in alkanes. 

Where A was derived from experimental log P measurements in an alkane-water system (i.e., cyclohexane/water) and the computed molar volumes (Eq. 9) ... 

The catalytic systems described here are liquid triphasic ones, with a heterogeneous catalyst such as supported noble metals (Pt, Pd), or high-surface-area metals (Raney-Ni). The liquid phases are constituted by an alkane, water, and an ammonium salt. This kind of system was developed over the past 12 years, initially as an efficient and mild catalytic methodology for the hydrodehalogena-tion reaction of haloaromatics, after which it was sffidied for other kinds of reactions, and careful observation has resulted in a theory of modes of action whereby reaction rates, and selectivity, could be intensified. 

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